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In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4 / Fabián Alberto Jaimes Barragán    

Público ISBD Título : In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4 Tipo de documento : documento electrónico Autores : Fabián Alberto Jaimes Barragán, Fecha de publicación : 2013 Títulos uniformes : AIDS Research and Therapy Idioma : Inglés (eng) Palabras clave : HIV infection  statins  CCR5  CXCR4  viral tropism  chemokines Resumen : Background: During the HIV-1 replication cycle, several molecules including chemokine receptors and cholesterol are crucial, and are therefore potential targets for therapeutic intervention. Indeed statins, compounds that inhibit cellular synthesis of cholesterol and have anti-inflammatory and immunomodulatory properties were shown to inhibit HIV-1 infection by R5 tropic strains but not by X4 strains in vitro, mainly by altering the chemokine receptor/ ligands axes. Therefore, the objective of this study was to characterize in vivo, the capacity of statins to modulate in HIV seronegative and chronically HIV-1-infected adults the expression of CCR5 and CXCR4, of their ligands and the tropism of circulating HIV-1 strains. Methods: Samples from asymptomatic HIV-1-infected adults enrolled in a clinical trial aimed at evaluating the antiretroviral activity of lovastatin were used to evaluate in vivo the modulation by lovastatin of CCR5, CXCR4, their ligands, and the shift in plasma viral tropism over one year of intervention. In addition, ten HIV negative adults received a daily oral dose of 40 mg of lovastatin or 20 mg of atorvastatin; seven other HIV negative individuals who received no treatment were followed as controls. The frequency and phenotype of immune cells were determined by flow-cytometry; mRNA levels of chemokine receptors and their ligands were determined by real-time PCR. Viral tropism was determined by PCR and sequencing, applying the clonal and clinical model of analyses. Results: Our study shows that long-term administration of lovastatin in HIV-infected individuals does not induce a shift in viral tropism, or induce a significant modulation of CCR5 and CXCR4 on immune cells in HIV-infected patients. Similar results were found in HIV seronegative control subjects, treated with lovastatin or atorvastatin, but a significant increase in CCL3 and CCL4 transcription was observed in these individuals. Conclusions: These findings suggest that long-term administration of statins at therapeutic doses, does not significantly affect the expression of HIV-1 co-receptors or of their ligands. In addition it is important to point out that based on the results obtained, therapeutic administration of statins in HIV-infected patients with lipid disorders is safe in terms of selecting X4 strains. Mención de responsabilidad : Edwin A Higuita, Fabián A Jaimes, Maria T Rugeles, Carlos J Montoya Referencia : AIDS Res Ther. 2013 May 1;10:10. DOI (Digital Object Identifier) : 10.1186/1742-6405-10-10 PMID : 23634877 Derechos de uso : CC BY En línea : https://aidsrestherapy.biomedcentral.com/articles/10.1186/1742-6405-10-10 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3691 In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4 [documento electrónico] / Fabián Alberto Jaimes Barragán,  . - 2013. Obra : AIDS Research and Therapy Idioma : Inglés (eng) Palabras clave : HIV infection  statins  CCR5  CXCR4  viral tropism  chemokines Resumen : Background: During the HIV-1 replication cycle, several molecules including chemokine receptors and cholesterol are crucial, and are therefore potential targets for therapeutic intervention. Indeed statins, compounds that inhibit cellular synthesis of cholesterol and have anti-inflammatory and immunomodulatory properties were shown to inhibit HIV-1 infection by R5 tropic strains but not by X4 strains in vitro, mainly by altering the chemokine receptor/ ligands axes. Therefore, the objective of this study was to characterize in vivo, the capacity of statins to modulate in HIV seronegative and chronically HIV-1-infected adults the expression of CCR5 and CXCR4, of their ligands and the tropism of circulating HIV-1 strains. Methods: Samples from asymptomatic HIV-1-infected adults enrolled in a clinical trial aimed at evaluating the antiretroviral activity of lovastatin were used to evaluate in vivo the modulation by lovastatin of CCR5, CXCR4, their ligands, and the shift in plasma viral tropism over one year of intervention. In addition, ten HIV negative adults received a daily oral dose of 40 mg of lovastatin or 20 mg of atorvastatin; seven other HIV negative individuals who received no treatment were followed as controls. The frequency and phenotype of immune cells were determined by flow-cytometry; mRNA levels of chemokine receptors and their ligands were determined by real-time PCR. Viral tropism was determined by PCR and sequencing, applying the clonal and clinical model of analyses. Results: Our study shows that long-term administration of lovastatin in HIV-infected individuals does not induce a shift in viral tropism, or induce a significant modulation of CCR5 and CXCR4 on immune cells in HIV-infected patients. Similar results were found in HIV seronegative control subjects, treated with lovastatin or atorvastatin, but a significant increase in CCL3 and CCL4 transcription was observed in these individuals. Conclusions: These findings suggest that long-term administration of statins at therapeutic doses, does not significantly affect the expression of HIV-1 co-receptors or of their ligands. In addition it is important to point out that based on the results obtained, therapeutic administration of statins in HIV-infected patients with lipid disorders is safe in terms of selecting X4 strains. Mención de responsabilidad : Edwin A Higuita, Fabián A Jaimes, Maria T Rugeles, Carlos J Montoya Referencia : AIDS Res Ther. 2013 May 1;10:10. DOI (Digital Object Identifier) : 10.1186/1742-6405-10-10 PMID : 23634877 Derechos de uso : CC BY En línea : https://aidsrestherapy.biomedcentral.com/articles/10.1186/1742-6405-10-10 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3691

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Randomized clinical trial of lovastatin in HIV-infected, HAART naïve patients (NCT00721305) / Fabián Alberto Jaimes Barragán ; Alba L. León  

Público ISBD Título : Randomized clinical trial of lovastatin in HIV-infected, HAART naïve patients (NCT00721305) Tipo de documento : documento electrónico Autores : Fabián Alberto Jaimes Barragán, ; Alba L. León, Fecha de publicación : 2012 Títulos uniformes : Journal of Infection Idioma : Inglés (eng) Palabras clave : HIV infection  anti-HIV agents  statin  lovastatin  randomized controlled trial Resumen : Background: Evidence suggests that statins may modify the immune response against HIV. The aim was to evaluate the antiretroviral and immunomodulatory effects of lov-astatin in HIV-infected patients, na€ıve for antiretroviral therapy. Methods: Randomized, double-blinded, placebo-controlled, phase-II clinical trial. Primary outcomes were plasma viral load and circulating CD4þ T cell count, after 6 and 12 months of treatment; secondary outcomes were CD8þ T cell count, expression of activation markers (CD38 and HLA-DR) on T cells, and clinical outcomes. With a power of 90% to detect both a decrease of 0.3 log10 in plasma HIV-1 RNA copies and an increase of 20% in the CD4þ T cell count, we estimated a required sample size of 110 HIV-infected patients (55 per group). The results were analyzed by a model of repeated measurements using Generalized Estimating Equations. Results: Patients were randomized to receive either lovastatin (n Z 55) or placebo (n Z 57). During the 12-month follow-up, there was no effect of lovastatin either on viral load (estimated average change Z 0.157 copies/mL; CI 95% Z 0.099 to 0.414), or on the CD4þ T cell count (estimated average change Z 26.1 cells/mL; CI 95% Z 89.8 to 37.6). Moreover, there were no significant differences in secondary outcomes. Conclusions: Daily administration of lovastatin (40 mg) for one year in HIV-infected patients, na€ıve for antiretroviral therapy, had no significant effect on HIV replication, the CD4þ T cell count, or the activation level of T cells. Mención de responsabilidad : Carlos J Montoya, Edwin A Higuita, Santiago Estrada, Francisco J Gutierrez, Pedro Amariles, Newar A Giraldo, Margarita M Jimenez, Claudia P Velasquez, Alba L Leon, Maria T Rugeles, Fabian A Jaimes Referencia : J Infect. 2012 Dec;65(6):549-58. DOI (Digital Object Identifier) : 10.1016/j.jinf.2012.10.016 PMID : 23085245 En línea : https://linkinghub.elsevier.com/retrieve/pii/S0163-4453(12)00302-7 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3602 Randomized clinical trial of lovastatin in HIV-infected, HAART naïve patients (NCT00721305) [documento electrónico] / Fabián Alberto Jaimes Barragán, ; Alba L. León,  . - 2012. Obra : Journal of Infection Idioma : Inglés (eng) Palabras clave : HIV infection  anti-HIV agents  statin  lovastatin  randomized controlled trial Resumen : Background: Evidence suggests that statins may modify the immune response against HIV. The aim was to evaluate the antiretroviral and immunomodulatory effects of lov-astatin in HIV-infected patients, na€ıve for antiretroviral therapy. Methods: Randomized, double-blinded, placebo-controlled, phase-II clinical trial. Primary outcomes were plasma viral load and circulating CD4þ T cell count, after 6 and 12 months of treatment; secondary outcomes were CD8þ T cell count, expression of activation markers (CD38 and HLA-DR) on T cells, and clinical outcomes. With a power of 90% to detect both a decrease of 0.3 log10 in plasma HIV-1 RNA copies and an increase of 20% in the CD4þ T cell count, we estimated a required sample size of 110 HIV-infected patients (55 per group). The results were analyzed by a model of repeated measurements using Generalized Estimating Equations. Results: Patients were randomized to receive either lovastatin (n Z 55) or placebo (n Z 57). During the 12-month follow-up, there was no effect of lovastatin either on viral load (estimated average change Z 0.157 copies/mL; CI 95% Z 0.099 to 0.414), or on the CD4þ T cell count (estimated average change Z 26.1 cells/mL; CI 95% Z 89.8 to 37.6). Moreover, there were no significant differences in secondary outcomes. Conclusions: Daily administration of lovastatin (40 mg) for one year in HIV-infected patients, na€ıve for antiretroviral therapy, had no significant effect on HIV replication, the CD4þ T cell count, or the activation level of T cells. Mención de responsabilidad : Carlos J Montoya, Edwin A Higuita, Santiago Estrada, Francisco J Gutierrez, Pedro Amariles, Newar A Giraldo, Margarita M Jimenez, Claudia P Velasquez, Alba L Leon, Maria T Rugeles, Fabian A Jaimes Referencia : J Infect. 2012 Dec;65(6):549-58. DOI (Digital Object Identifier) : 10.1016/j.jinf.2012.10.016 PMID : 23085245 En línea : https://linkinghub.elsevier.com/retrieve/pii/S0163-4453(12)00302-7 Enlace permanente : https://hospitalpablotobon.cloudbiteca.com/pmb/opac_css/index.php?lvl=notice_display&id=3602

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